Dissecting genetics of spectrum of epilepsies with eyelid myoclonia by exome sequencing.

Autor: Coppola A; Department of Neuroscience, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy., Krithika S; Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK.; Chalfont Centre for Epilepsy, Chalfont St Peter, UK.; School of Life Sciences, Anglia Ruskin University, Cambridge, UK., Iacomino M; Unit of Medical Genetics, IRCCS Istituto Giannina Gaslini, Genoa, Italy., Bobbili D; Bioinformatics Core, Luxembourg Center for Systems Biomedicine, Belvaux, Luxembourg., Balestrini S; Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK.; Chalfont Centre for Epilepsy, Chalfont St Peter, UK.; Neuroscience Department, Meyer Children's Hospital-University of Florence, Florence, Italy., Bagnasco I; Division of Child Neuropsychiatry, Martini Hospital, Turin, Italy., Bilo L; Department of Neuroscience, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy., Buti D; Pediatric Neurology Unit and Laboratories, Meyer Children's Hospital-University of Florence, Florence, Italy., Casellato S; Unit of Child Neuropsychiatry, University Hospital of Sassari, Sassari, Italy., Cuccurullo C; Department of Neuroscience, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy., Ferlazzo E; Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Regional Epilepsy Center, Great Metropolitan Hospital, Bianchi-Melacrino Morelli, Reggio Calabria, Italy., Leu C; Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK.; Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.; Stanley Center of Psychiatric Research, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, USA., Giordano L; Unit of Child Neurology and Psychiatry, ASST Spedali Civili di Brescia, Brescia, Italy., Gobbi G; Child Neurology Unit, IRCCS Istituto delle Scienze Neurologiche, Bologna, Italy., Hernandez-Hernandez L; Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK.; Chalfont Centre for Epilepsy, Chalfont St Peter, UK., Lench N; MRC Nucleic Acid Therapy Accelerator, Research Complex at Harwell, Rutherford Appleton Laboratory, Harwell, UK., Martins H; Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK.; Chalfont Centre for Epilepsy, Chalfont St Peter, UK., Meletti S; Department of Biomedical, Metabolic, and Neural Science, University of Modena and Reggio Emilia, Modena, Italy.; Neurology Unit, OCB Hospital, Azienda Ospedaliera Universitaria di Modena, Modena, Italy., Messana T; IRCCS Istituto delle Scienze Neurologiche di Bologna, UOC Neuropsichiatria Infantile, Bologna, Italy., Nigro V; Telethon Institute of Genetics and Medicine, Naples, Italy., Pinelli M; Telethon Institute of Genetics and Medicine, Naples, Italy., Pippucci T; Computational Genomics Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy., Bellampalli R; Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK.; Chalfont Centre for Epilepsy, Chalfont St Peter, UK., Salis B; Unit of Child Neuropsychiatry, ASST Fatebenefratelli Sacco, Milan, Italy., Sofia V; Department of Medical and Surgical Sciences and Advanced Technologies 'G.F. Ingrassia,' Section of Neurosciences, University of Catania, Catania, Italy., Striano P; Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy., Striano S; Department of Neuroscience, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy., Tassi L; 'Claudio Munari' Epilepsy Surgery Center, Niguarda Hospital, Milan, Italy., Vignoli A; Department of Health Sciences, Università degli Studi di Milano, Milan, Italy., Vaudano AE; Department of Biomedical, Metabolic, and Neural Science, University of Modena and Reggio Emilia, Modena, Italy.; Neurology Unit, OCB Hospital, Azienda Ospedaliera Universitaria di Modena, Modena, Italy., Viri M; Department of Child Neurology and Psychiatry, AOU Maggiore della Carità Novara, Novara, Italy., Scheffer IE; Department of Medicine, Austin Health, Epilepsy Research Center, University of Melbourne, Heidelberg, Victoria, Australia.; Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia.; Murdoch Children's Research Institute and Department of Paediatrics, Royal Children's Hospital, University of Melbourne, Parkville, Victoria, Australia., May P; Bioinformatics Core, Luxembourg Center for Systems Biomedicine, Belvaux, Luxembourg., Zara F; Unit of Medical Genetics, IRCCS Istituto Giannina Gaslini, Genoa, Italy.; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy., Sisodiya SM; Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK.; Chalfont Centre for Epilepsy, Chalfont St Peter, UK.
Jazyk: angličtina
Zdroj: Epilepsia [Epilepsia] 2024 Mar; Vol. 65 (3), pp. 779-791. Date of Electronic Publication: 2023 Dec 23.
DOI: 10.1111/epi.17859
Abstrakt: Objective: Epilepsy with eyelid myoclonia (EEM) spectrum is a generalized form of epilepsy characterized by eyelid myoclonia with or without absences, eye closure-induced seizures with electroencephalographic paroxysms, and photosensitivity. Based on the specific clinical features, age at onset, and familial occurrence, a genetic cause has been postulated. Pathogenic variants in CHD2, SYNGAP1, NEXMIF, RORB, and GABRA1 have been reported in individuals with photosensitivity and eyelid myoclonia, but whether other genes are also involved, or a single gene is uniquely linked with EEM, or its subtypes, is not yet known. We aimed to dissect the genetic etiology of EEM.
Methods: We studied a cohort of 105 individuals by using whole exome sequencing. Individuals were divided into two groups: EEM- (isolated EEM) and EEM+ (EEM accompanied by intellectual disability [ID] or any other neurodevelopmental/psychiatric disorder).
Results: We identified nine variants classified as pathogenic/likely pathogenic in the entire cohort (8.57%); among these, eight (five in CHD2, one in NEXMIF, one in SYNGAP1, and one in TRIM8) were found in the EEM+ subcohort (28.57%). Only one variant (IFIH1) was found in the EEM- subcohort (1.29%); however, because the phenotype of the proband did not fit with published data, additional evidence is needed before considering IFIH1 variants and EEM- an established association. Burden analysis did not identify any single burdened gene or gene set.
Significance: Our results suggest that for EEM, as for many other epilepsies, the identification of a genetic cause is more likely with comorbid ID and/or other neurodevelopmental disorders. Pathogenic variants were mostly found in CHD2, and the association of CHD2 with EEM+ can now be considered a reasonable gene-disease association. We provide further evidence to strengthen the association of EEM+ with NEXMIF and SYNGAP1. Possible new associations between EEM+ and TRIM8, and EEM- and IFIH1, are also reported. Although we provide robust evidence for gene variants associated with EEM+, the core genetic etiology of EEM- remains to be elucidated.
(© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)
Databáze: MEDLINE
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